Distinct lipid transport proteins are regulated by innate immune stimuli
File(s)
Published version
Author(s)
Tsamouri, Lydia
Aljadeed, Najd
Olona, Antoni
Anand, Paras
Type
Journal Article
Abstract
Lipid transport plays a critical role in the distribution of lipids across subcellular compartments. This is pivotal during infection and other stress stimuli that increase metabolic demands. While lipid biosynthesis is regulated by immune stimuli, whether immune signalling also influences lipid transport mechanisms remains unexplored. Here, we demonstrate that TLR signalling
impacts the gene expression of lipid transport proteins in human monocytic THP-1 cell line and compare it to the expression in primary bone marrow-derived mouse macrophages. Our data demonstrates that TLR4 signalling selectively modulates the expression of oxysterol binding protein-related proteins (ORPs), a key family of proteins that transport lipids between
organelles. Remarkably, TLR4 activation led to the downregulation of several ORP family members in human THP1-derived macrophages. However, this response was less profound in mouse macrophages. In contrast, the expression of steroidogenic acute regulatory domain (STARD) proteins, many of which transport lipids between mitochondria and other
compartments, exhibited no statistical difference. Moreover, IFNG, a cytokine that plays a key role in the immune response, did not considerably impact human ORP or STARD expression levels, either alone or in combination with LPS. Together, these results reveal that TLR signalling exerts selective and critical control over lipid trafficking pathways with important biological differences. These findings provide new insights into the crosstalk between immune signalling and lipid metabolism, which may offer novel targets to treat diseases characterized by dysregulated lipid pathways.
impacts the gene expression of lipid transport proteins in human monocytic THP-1 cell line and compare it to the expression in primary bone marrow-derived mouse macrophages. Our data demonstrates that TLR4 signalling selectively modulates the expression of oxysterol binding protein-related proteins (ORPs), a key family of proteins that transport lipids between
organelles. Remarkably, TLR4 activation led to the downregulation of several ORP family members in human THP1-derived macrophages. However, this response was less profound in mouse macrophages. In contrast, the expression of steroidogenic acute regulatory domain (STARD) proteins, many of which transport lipids between mitochondria and other
compartments, exhibited no statistical difference. Moreover, IFNG, a cytokine that plays a key role in the immune response, did not considerably impact human ORP or STARD expression levels, either alone or in combination with LPS. Together, these results reveal that TLR signalling exerts selective and critical control over lipid trafficking pathways with important biological differences. These findings provide new insights into the crosstalk between immune signalling and lipid metabolism, which may offer novel targets to treat diseases characterized by dysregulated lipid pathways.
Date Issued
2026-07-15
Date Acceptance
2026-06-19
Citation
Discovery Immunology, 2026, 5 (1)
ISSN
2754-2483
Publisher
Oxford University Press
Journal / Book Title
Discovery Immunology
Volume
5
Issue
1
Copyright Statement
© The Author(s) 2026. Published by Oxford University Press on behalf of the British Society of Immunology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
10.1093/discim/kyag014
Subjects
lipids
lipid transport proteins
ORP
STARD
immune signalling
Publication Status
Published
Article Number
kyag014
Date Publish Online
2026-07-02